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1.
Front Immunol ; 15: 1277074, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915405

RESUMO

Garlic (Allium sativum L.) is a widely abundant spice, known for its aroma and pungent flavor. It contains several bioactive compounds and offers a wide range of health benefits to humans, including those pertaining to nutrition, physiology, and medicine. Therefore, garlic is considered as one of the most effective disease-preventive diets. Many in vitro and in vivo studies have reported the sulfur-containing compounds, allicin and ajoene, for their effective anticancer, anti-diabetic, anti-inflammatory, antioxidant, antimicrobial, immune-boosting, and cardioprotective properties. As a rich natural source of bioactive compounds, including polysaccharides, saponins, tannins, linalool, geraniol, phellandrene, ß-phellandrene, ajoene, alliin, S-allyl-mercapto cysteine, and ß-phellandrene, garlic has many therapeutic applications and may play a role in drug development against various human diseases. In the current review, garlic and its major bioactive components along with their biological function and mechanisms of action for their role in disease prevention and therapy are discussed.


Assuntos
Alho , Alho/química , Humanos , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/farmacologia , Ácidos Sulfínicos/uso terapêutico , Ácidos Sulfínicos/farmacologia , Dissulfetos
2.
Ecotoxicol Environ Saf ; 280: 116527, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38833978

RESUMO

Aflatoxin B1 (AFB1) is known to inhibit growth, and inflict hepatic damage by interfering with protein synthesis. Allicin, has been acknowledged as an efficacious antioxidant capable of shielding the liver from oxidative harm. This study aimed to examine the damage caused by AFB1 on bovine hepatic cells and the protective role of allicin against AFB1-induced cytotoxicity. In this study, cells were pretreated with allicin before the addition of AFB1 for co-cultivation. Our findings indicate that AFB1 compromises cellular integrity, suppresses the expression of nuclear factor erythroid 2-related factor 2 (Nrf2). In addition, allicin attenuates oxidative damage to bovine hepatic cells caused by AFB1 by promoting the expression of the Nrf2 pathway and reducing cell apoptosis. In conclusion, the results of this study will help advance clinical research and applications, providing new options and directions for the prevention and treatment of liver diseases.


Assuntos
Aflatoxina B1 , Antioxidantes , Apoptose , Dissulfetos , Hepatócitos , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Transdução de Sinais , Ácidos Sulfínicos , Animais , Ácidos Sulfínicos/farmacologia , Aflatoxina B1/toxicidade , Bovinos , Dissulfetos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Antioxidantes/farmacologia , Feminino
3.
Tissue Cell ; 88: 102398, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38728949

RESUMO

BACKGROUND: Allicin regulates macrophage autophagy and senescence, and inhibits hepatoma cell growth. This study investigated the mechanism by which allicin inhibits the growth of hepatoma cells. METHODS: Hepa1-6 mouse hepatoma cells were subcutaneously injected into C57BL/6 J mice to construct a tumor transplantation model. Macrophages were cultured with the supernatant of hepatoma cells to construct a cell model. The levels of mRNA and proteins and the level of Sestrin2 ubiquitination were measured by RTqPCR, immunofluorescence and Western blotting. The levels of autophagy-related factors and the activity of senescence-associated ß-galactosidase were determined by kits, and protein stability was detected by cycloheximide (CHX) tracking. RESULTS: Data analysis of clinical samples revealed that RBX1 was highly expressed in tumor tissues, while Sestrin2 was expressed at low levels in tumor tissues. Allicin can promote the expression of the autophagy-related proteins LC3 and Beclin-1 in tumor macrophages and inhibit the expression of the aging-related proteins p16 and p21, thus promoting autophagy in macrophages and inhibiting cell senescence. Moreover, allicin can inhibit the expression of RBX1, thereby reducing the ubiquitination of Sestrin2, enhancing the stability of Sestrin2, activating autophagy in tumor macrophages and inhibiting senescence. In addition, allicin treatment inhibited the proliferation and migration of hepatoma carcinoma cells cocultured with macrophages and significantly improved the development of liver cancer in mice. CONCLUSION: Allicin can affect the autophagy of macrophages and restrain the growth of hepatoma cells by regulating the ubiquitination of Sestrin2.


Assuntos
Autofagia , Carcinoma Hepatocelular , Senescência Celular , Dissulfetos , Neoplasias Hepáticas , Macrófagos , Ácidos Sulfínicos , Ubiquitinação , Animais , Autofagia/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Dissulfetos/farmacologia , Senescência Celular/efeitos dos fármacos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Ácidos Sulfínicos/farmacologia , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Linhagem Celular Tumoral , Ubiquitinação/efeitos dos fármacos , Humanos , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Proteínas Nucleares/metabolismo , Masculino , Peroxidases/metabolismo , Sestrinas
4.
J Agric Food Chem ; 72(23): 13228-13239, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38810088

RESUMO

Limited alliinase resources cause difficulties in the biosynthesis of thiosulfinates (e.g., allicin), restricting their applications in the agricultural and food industries. To effectively biosynthesize thiosulfinates, this study aimed to excavate bacterial alliinase resources and elucidate their catalytic properties. Two bacterial cystathionine ß-lyases (MetCs) possessing high alliinase activity (>60 U mg -1) toward L-(-)-alliin were identified from Allium sativum rhizosphere isolates. Metagenomic exploration revealed that cystathionine ß-lyase from Bacillus cereus (BcPatB) possessed high activity toward both L-(±)-alliin and L-(+)-alliin (208.6 and 225.1 U mg -1), respectively. Although these enzymes all preferred l-cysteine S-conjugate sulfoxides as substrates, BcPatB had a closer phylogenetic relationship with Allium alliinases and shared several similar features with A. sativum alliinase. Interestingly, the Trp30Ile31Ala32Asp33 Met34 motif in a cuspate loop of BcPatB, especially sites 31 and 32 at the top of the motif, was modeled to locate near the sulfoxide of L-(+)-alliin and is important for substrate stereospecificity. Moreover, the stereoselectivity and activity of mutants I31V and A32G were higher toward L-(+)-alliin than those of mutant I31L/D33E toward L-(-)-alliin. Using bacterial alliinases and chemically synthesized substrates, we obtained thiosulfinates with high antimicrobial and antinematode activities that could provide insights into the protection of crops and food.


Assuntos
Proteínas de Bactérias , Alho , Especificidade por Substrato , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Alho/química , Alho/enzimologia , Alho/genética , Ácidos Sulfínicos/química , Ácidos Sulfínicos/metabolismo , Bacillus cereus/enzimologia , Bacillus cereus/genética , Bacillus cereus/metabolismo , Dissulfetos/química , Dissulfetos/metabolismo , Filogenia , Estereoisomerismo , Sequência de Aminoácidos , Bactérias/enzimologia , Bactérias/genética , Bactérias/classificação , Bactérias/metabolismo , Cinética , Liases de Carbono-Enxofre/metabolismo , Liases de Carbono-Enxofre/genética , Liases de Carbono-Enxofre/química , Cisteína/análogos & derivados
5.
Clin Transl Med ; 14(5): e1687, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38738791

RESUMO

OBJECTIVE: It has been observed that the prognosis of patients with HER2-positive metastatic breast cancer has improved significantly with HER2-targeted agents. However, there is still a lack of evidence regarding first-line anti-HER2 treatment options for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, there are no reliable markers that can predict the efficacy of anti-HER2 treatment in these patients. METHODS: Patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer were enrolled. Pyrotinib plus albumin-bound paclitaxel were used as first-line treatment. The primary endpoint was the objective response rate (ORR). The safety profile was also assessed. In order to explore predictive biomarkers using Olink technology, blood samples were collected dynamically. RESULTS: From December 2019 to August 2023, the first stage of the study involved 27 eligible patients. It has not yet reached the median PFS despite the median follow-up being 17.8 months. Efficacy evaluation showed that the ORR was 92.6%, and the DCR was 100%. Adverse events of grade 3 or higher included diarrhoea (29.6%), leukopenia (11.1%), neutropenia (25.9%), oral mucositis (3.7%), and hand-foot syndrome (3.7%). Toll-like receptor 3 (TLR3) and Proto-oncogene tyrosine-protein kinase receptor (RET) were proteins with significant relevance to PFS in these patients. CONCLUSIONS: This study demonstrates that pyrotinib plus albumin-bound paclitaxel as a first-line treatment regimen shows good efficacy and manageable safety for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, a significant association was identified between the expression levels of TLR3 and RET and the PFS in patients.


Assuntos
Neoplasias da Mama , Receptor ErbB-2 , Trastuzumab , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Pessoa de Meia-Idade , Adulto , Trastuzumab/uso terapêutico , Trastuzumab/farmacologia , Estudos Prospectivos , Idoso , Receptor ErbB-2/metabolismo , Paclitaxel Ligado a Albumina/uso terapêutico , Paclitaxel Ligado a Albumina/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Acrilamidas/uso terapêutico , Terapia Neoadjuvante/métodos , Proto-Oncogene Mas , Ácidos Sulfínicos/uso terapêutico , Ácidos Sulfínicos/farmacologia , Aminoquinolinas/uso terapêutico , Aminoquinolinas/farmacologia , Resultado do Tratamento
6.
Eur Rev Med Pharmacol Sci ; 28(7): 2817-2826, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38639521

RESUMO

OBJECTIVE: Testicular ischemia-reperfusion induced by testicular torsion-detorsion increases the level of reactive oxygen species, leading to testicular damage. Allicin, one of the most active ingredients in garlic, is a significant exogenous antioxidant. In the research, the efficacy of allicin in treating testicular ischemia-reperfusion injury was assessed. MATERIALS AND METHODS: The study included sixty Sprague-Dawley male rats. Three groups with 20 rats per group were created as follows: control group, testicular ischemia/reperfusion-induced group, and testicular ischemia-reperfusion plus treatment with allicin group. The control group underwent a sham operation of the left testis without other interventions. In the testicular ischemia/reperfusion-induced group, rat left testis was subjected to 720° torsion for two hours and then detorsion. In the allicin-treated group, in addition to testicular ischemia-reperfusion, 50 mg/kg of allicin was injected intraperitoneally, starting immediately following detorsion. Testicular tissue samples were obtained to measure the protein expression of xanthine oxidase, which is a major source of reactive oxygen species formation, malondialdehyde level (a reliable marker of reactive oxygen species), and testicular spermatogenic function. RESULTS: Testicular ischemia-reperfusion significantly increased the expression of xanthine oxidase and malondialdehyde levels in ipsilateral testes while reducing testicular spermatogenic function. The expression of xanthine oxidase and malondialdehyde levels were significantly lower in ipsilateral testes, whereas testicular spermatogenic function in the allicin-treated group was significantly higher compared with those in the testicular ischemia-reperfusion group. CONCLUSIONS: Our findings indicate that allicin administration improves ischemia/reperfusion-induced testicular damage by limiting reactive oxygen species generation via inhibition of xanthine oxidase expression.


Assuntos
Dissulfetos , Traumatismo por Reperfusão , Torção do Cordão Espermático , Ácidos Sulfínicos , Ratos , Masculino , Animais , Humanos , Torção do Cordão Espermático/tratamento farmacológico , Torção do Cordão Espermático/complicações , Torção do Cordão Espermático/metabolismo , Ratos Sprague-Dawley , Xantina Oxidase/metabolismo , Xantina Oxidase/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Testículo , Traumatismo por Reperfusão/metabolismo , Antioxidantes/farmacologia , Isquemia/metabolismo , Malondialdeído/metabolismo
7.
Chembiochem ; 25(9): e202400131, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38597743

RESUMO

Many actinobacterial species contain structural genes for iron-dependent enzymes that consume ergothioneine by way of O2-dependent dioxygenation. The resulting product ergothioneine sulfinic acid is stable under physiological conditions unless cleavage to sulfur dioxide and trimethyl histidine is catalyzed by a dedicated desulfinase. This report documents that two types of ergothioneine sulfinic desulfinases have evolved by convergent evolution. One type is related to metal-dependent decarboxylases while the other belongs to the superfamily of rhodanese-like enzymes. Pairs of ergothioneine dioxygenases (ETDO) and ergothioneine sulfinic acid desulfinase (ETSD) occur in thousands of sequenced actinobacteria, suggesting that oxidative ergothioneine degradation is a common activity in this phylum.


Assuntos
Ergotioneína , Ergotioneína/metabolismo , Ergotioneína/química , Actinobacteria/enzimologia , Biocatálise , Ácidos Sulfínicos/química , Ácidos Sulfínicos/metabolismo , Dioxigenases/metabolismo , Dioxigenases/química
8.
Mol Plant Microbe Interact ; 37(6): 507-519, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38489400

RESUMO

Burkholderia gladioli pv. alliicola, B. cepacia, and B. orbicola are common bacterial pathogens of onion. Onions produce organosulfur thiosulfinate defensive compounds after cellular decompartmentalization. Using whole-genome sequencing and in silico analysis, we identified putative thiosulfinate tolerance gene (TTG) clusters in multiple onion-associated Burkholderia species similar to those characterized in other Allium-associated bacterial endophytes and pathogens. Sequence analysis revealed the presence of three Burkholderia TTG cluster types, with both Type A and Type B being broadly distributed in B. gladioli, B. cepacia, and B. orbicola in both the chromosome and plasmids. Based on isolate natural variation and generation of isogenic strains, we determined the in vitro and in vivo contribution of TTG clusters in B. gladioli, B. cepacia, and B. orbicola. The Burkholderia TTG clusters contributed to enhanced allicin tolerance and improved growth in filtered onion extracts by all three species. TTG clusters also made clear contributions to B. gladioli foliar necrosis symptoms and bacterial populations. Surprisingly, the TTG cluster did not contribute to bacterial populations in onion bulb scales by these three species. Based on our findings, we hypothesize onion-associated Burkholderia may evade or inhibit the production of thiosulfinates in onion bulb tissues. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Assuntos
Burkholderia , Família Multigênica , Cebolas , Cebolas/microbiologia , Burkholderia/genética , Burkholderia/efeitos dos fármacos , Doenças das Plantas/microbiologia , Ácidos Sulfínicos/farmacologia
9.
Aging (Albany NY) ; 16(6): 5207-5223, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38460945

RESUMO

OBJECTIVE: The study attempted to explore how allicin reduces oxidative stress levels by promoting SHP2 expression to inhibit p-PERK in I/R mice. METHODS: The GEO database and RNA sequencing were used to predict downstream gene. TTC staining was used to visualize the myocardial infarction area. Masson staining was used to assess the level of fibrosis. IF was used to examine the expression of SHP2, CTGF, ROS. RT-PCR analysis was used to quantify the expression of SHP2 mRNA. Western blot was used to detect the protein expression levels of SHP2, p-PERK, MFN1, NLRP3, NOX2, and NOX3. RESULTS: GEO and transcriptomic data revealed low expression of SHP2 in the heart tissues I/R mice. In the I/R mouse model, TTC staining result showed that allicin can reduce the area of myocardial infarction; Masson staining results indicated that allicin can reduce fibrosis; Macrophage transcriptome sequencing found SHP2 is a target gene of allicin; Immunofluorescence showed allicin can increase SHP2; qPCR results showed allicin can raise SHP2 mRNA level; Immunofluorescence indicated that allicin can inhibit ROS in myocardial infarction tissue, but the specific SHP2-KD eliminates changes in ROS. Western blot analysis demonstrated allicin can increase SHP2 protein and reduce the expression of p-PERK, MFN1, NLRP3, NOX2, and NOX3; SHP2-KD eliminates the expression differences in p-PERK, MFN1, NLRP3, NOX2, and NOX3. CONCLUSIONS: Allicin can modulate p-PERK activation by enhancing the expression of SHP2, thereby inhibiting myocardial ischemia-reperfusion-induced oxidative stress in mice.


Assuntos
Dissulfetos , Infarto do Miocárdio , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ácidos Sulfínicos , Camundongos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo , Infarto do Miocárdio/tratamento farmacológico , Fibrose , RNA Mensageiro/metabolismo
10.
J Chromatogr A ; 1721: 464819, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38537485

RESUMO

Silanophilic interactions are a primary contributor to peak tailing of acidic pharmaceutical compounds, thus a thorough understanding is especially important for reversed-phase liquid chromatography (RPLC) method development. Herein, a sulfinic acid compound that exhibited severe peak tailing in RPLC with acidic mobile phases was carefully studied. Results indicated that the neutral protonated form of the sulfinic acid is involved in the strong interaction that leads to peak tailing, but that tailing can be mitigated with a blocking effect achieved through use of acetic acid modifier in the mobile phase. Peak tailing was also observed with other structurally-similar sulfinic acids and carboxylic acids but was, in general, less severe with the latter. The Hydrophobic Subtraction Model (HSM) was applied to six commercial C18 columns that exhibited different tailing behaviors for the sulfinic acid compound in attempts to identify key sites of interaction within the stationary phase. A combination of heated acid column wash experiments and density functional theory (DFT) calculations indicate that the differential interactions of the acids with vicinal silanol pairs in the stationary phase play a major role in peak tailing.


Assuntos
Cromatografia de Fase Reversa , Ácidos Sulfínicos , Cromatografia de Fase Reversa/métodos , Ácidos Carboxílicos , Indicadores e Reagentes , Ácido Acético , Cromatografia Líquida de Alta Pressão/métodos
11.
J Med Chem ; 67(6): 4641-4654, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38478885

RESUMO

Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules that have emerged as a therapeutic modality to induce targeted protein degradation (TPD) by harnessing cellular proteolytic degradation machinery. PROTACs which ligand the E3 ligase in a covalent manner have attracted intense interest; however, covalent PROTACs with a broad protein of interest (POI) scope have proven challenging to discover by design. Here, we report the structure-guided design and optimization of Von Hippel-Lindau (VHL) protein-targeted sulfonyl fluorides which covalently bind Ser110 in the HIF1α binding site. We demonstrate that their incorporation in bifunctional degraders induces targeted protein degradation of BRD4 or the androgen receptor without further linker optimization. Our study discloses the first covalent VHL ligands which can be implemented directly in bifunctional degrader design, expanding the substrate scope of covalent E3 ligase PROTACs.


Assuntos
Proteínas Nucleares , Ácidos Sulfínicos , Fatores de Transcrição , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteólise , Ligantes
12.
Molecules ; 29(6)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38542956

RESUMO

Natural products, particularly medicinal plants, are crucial in combating cancer and aiding in the discovery and development of new therapeutic agents owing to their biologically active compounds. They offer a promising avenue for developing effective anticancer medications because of their low toxicity, diverse chemical structures, and ability to target various cancers. Allicin is one of the main ingredients in garlic (Allium sativum L.). It is a bioactive sulfur compound maintained in various plant sections in a precursor state. Numerous studies have documented the positive health benefits of this natural compound on many chronic conditions, including gastric, hepatic, breast, lung, cervical, prostate, and colon cancer. Moreover, allicin may target several cancer hallmarks or fundamental biological traits and functions that influence cancer development and spread. Cancer hallmarks include sustained proliferation, evasion of growth suppressors, metastasis, replicative immortality, angiogenesis, resistance to cell death, altered cellular energetics, and immune evasion. The findings of this review should provide researchers and medical professionals with a solid basis to support fundamental and clinical investigations of allicin as a prospective anticancer drug. This review outlines the anticancer role of allicin in each hallmark of cancer.


Assuntos
Antineoplásicos , Neoplasias do Colo , Alho , Plantas Medicinais , Masculino , Humanos , Extratos Vegetais/química , Estudos Prospectivos , Ácidos Sulfínicos/química , Dissulfetos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Alho/química
13.
Mol Nutr Food Res ; 68(5): e2300622, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38339885

RESUMO

SCOPE: Allicin, a product of enzymatic reaction when garlic is injured, plays an important role in maintaining glucose homeostasis in mammals. However, the effect of allicin on glucose homeostasis in the state of insulin resistance remains to be elucidated. This study investigates the effect of allicin on glucose metabolism using different muscle fibers in a chicken model. METHODS AND RESULTS: Day-old male Arbor Acres broilers are randomly divided into three groups and fed a basal diet supplemented with 0, 150, or 300 mg kg-1 allicin for 42 days. Results show that allicin improves the zootechnical performance of broilers at the finishing stage. The glucose loading test (2 g kg-1 body mass) indicates the regulatory role of allicin on glucose homeostasis. In vitro results demonstrate allicin increases glutathione (GSH) level and the expression of cystathionine γ lyase (CSE), leading to endogenous hydrogen sulfide (H2S) production in M. pectoralis major (PM) muscle-derived myotubes. Allicin stimulates adenosine monophosphate-activated protein kinase (AMPK) S-sulfhydration and AMPK phosphorylation to promote glucose uptake, which is suppressed in the presence of d,l-propargylglycine (PAG, a CSE inhibitor). CONCLUSION: This study demonstrates that allicin induces AMPK S-sulfhydration and AMPK phosphorylation to promote glucose uptake via the CSE/H2S system in a muscle fiber-dependent manner.


Assuntos
Galinhas , Dissulfetos , Sulfeto de Hidrogênio , Ácidos Sulfínicos , Masculino , Animais , Galinhas/metabolismo , Proteínas Quinases Ativadas por AMP , Fibras Musculares Esqueléticas/metabolismo , Glucose/metabolismo , Sulfeto de Hidrogênio/metabolismo , Mamíferos/metabolismo
14.
Anim Sci J ; 95(1): e13917, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38323750

RESUMO

Allicin is a sulfur-containing compound extracted from raw garlic (Allium sativum L.). We compared the effect of allicin addition on growth performance, serum biochemical parameters, and rumen microbiota of goats compared to monensin. Twenty-four Anhui white goats were assigned randomly to one of three dietary treatments: 1) a basal diet (CON); 2) the basal diet with allicin addition at 750 mg per head per day (AC); 3) the basal diet with monensin addition at 30 mg per kg of diet (MS). Animals were fed for 8 weeks. Results showed the average daily gain, and feed efficiency was increased with allicin and monensin addition. Serum levels of IgG, total superoxide dismutase, and glutathione peroxidase were higher in the AC group than those in the CON and MS groups. The microbiota analysis revealed that monensin addition mainly affected genera related to carbohydrate and protein metabolism, and allicin mainly affected genera related to energy metabolism and intestinal health. In conclusion, allicin could improve growth performance and have advantages over monensin in improving the antioxidant capacity and immune function of goats. Allicin may be a potential alternative to monensin.


Assuntos
Dissulfetos , Alho , Microbiota , Ácidos Sulfínicos , Animais , Ração Animal/análise , Antioxidantes/metabolismo , Dieta/veterinária , Suplementos Nutricionais/análise , Cabras/metabolismo , Monensin/farmacologia , Rúmen/metabolismo
15.
Naunyn Schmiedebergs Arch Pharmacol ; 397(2): 703-724, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37615709

RESUMO

The main objective of this review is to highlight the therapeutic potential of allicin, a defense molecule in garlic known for its diverse health benefits, and address the key challenges of its bioavailability and stability. The research further aims to evaluate various formulation strategies and nanotechnology-based delivery systems that can resolve these issues and improve allicin's clinical efficacy, especially in cancer therapy. We conducted a comprehensive review of the available literature and previous studies, focusing on the therapeutic properties of allicin, its bioavailability, stability issues, and novel formulation strategies. We assessed the mechanism of action of allicin in cancer, including its effects on signaling pathways, cell cycle, apoptosis, autophagy, and tumor development. We also evaluated the outcomes of both in vitro and in vivo studies on different types of cancers, such as breast, cervical, colon, lung, and gastric cancer. Despite allicin's significant therapeutic benefits, including cardiovascular, antihypertensive, cholesterol-lowering, antimicrobial, antifungal, anticancer, and immune-modulatory activity, its clinical utility is limited due to poor stability and unpredictable bioavailability. Allicin's bioavailability in the gastrointestinal tract is dependent on the activity of the enzyme alliinase, and its stability can be affected by various conditions like gastric acid and intestinal enzyme proteases. Recent advances in formulation strategies and nanotechnology-based drug delivery systems show promise in addressing these challenges, potentially improving allicin's solubility, stability, and bioavailability. Allicin offers substantial potential for cancer therapy, yet its application is hindered by its instability and poor bioavailability. Novel formulation strategies and nanotechnology-based delivery systems can significantly overcome these limitations, enhancing the therapeutic efficacy of allicin. Future research should focus on refining these formulation strategies and delivery systems, ensuring the safety and efficacy of these new allicin formulations. Clinical trials and long-term studies should be carried out to determine the optimal dosage, assess potential side effects, and evaluate their real-world applicability. The comparative analysis of different drug delivery approaches and the development of targeted delivery systems can also provide further insight into enhancing the therapeutic potential of allicin.


Assuntos
Dissulfetos , Neoplasias , Humanos , Disponibilidade Biológica , Ácidos Sulfínicos/uso terapêutico , Ácidos Sulfínicos/metabolismo , Ácidos Sulfínicos/farmacologia , Resultado do Tratamento , Neoplasias/tratamento farmacológico
16.
J Econ Entomol ; 117(1): 1-7, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-37972274

RESUMO

Sulfuryl fluoride (SF) is a fumigant used to eliminate drywood termites (DWT: Kalotermitidae; Froggatt) and other structural pests. Because of its global warming potential, it has been suggested that SF be restricted as a greenhouse gas (GHG). We present an economic model to assess the net social cost of restricting SF. We consider 3 approaches to address DWT control- no treatment, allowing SF fumigation and localized treatments, and only local treatment. Each approach generates private and public benefits and costs. We estimate that the annual damage and home equity loss by DWT in California is US$4.5-16.8 billion without treatment. If fumigation is used on 20% of the houses and local treatments on the others, the combined social cost of treatment, damage, and GHG emissions are between US$1-US$2 billion annually. The annual cost of local treatments only would be between US$3.2 and US$4.9 billion. If the application of SF is severely restricted or banned, the social costs will increase between US$1.43 and US$4.31 billion annually. The implied cost per ton of CO2 eliminated is between US$624 and US$1,465, much above the price range of CO2 in other applications. The restriction/ban has significant equity and environmental effects, impacting low-income individuals living in rented properties and replacing damaged wood in housing will increase GHG emissions. We further recommend the continued use of SF until a comparable whole-structure alternative is developed that fits the parameters of our model.


Assuntos
Baratas , Isópteros , Praguicidas , Ácidos Sulfínicos , Animais , Dióxido de Carbono
17.
Int J Mol Sci ; 24(24)2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38139348

RESUMO

Invasive fungal (IF) diseases are a leading global cause of mortality, particularly among immunocompromised individuals. The SARS-CoV-2 pandemic further exacerbated this scenario, intensifying comorbid IF infections such as mucormycoses of the nasopharynx. In the work reported here, it is shown that zygomycetes, significant contributors to mycoses, are sensitive to the natural product allicin. Inhibition of Mucorales fungi by allicin in solution and by allicin vapor was demonstrated. Mathematical modeling showed that the efficacy of allicin vapor is comparable to direct contact with the commercially available antifungal agent amphotericin B (ampB). Furthermore, the study revealed a synergistic interaction between allicin and the non-volatile ampB. The toxicity of allicin solution to human cell lines was evaluated and it was found that the half maximal effective concentration (EC50) of allicin was 25-72 times higher in the cell lines as compared to the fungal spores. Fungal allicin sensitivity depends on the spore concentration, as demonstrated in a drop test. This study shows the potential of allicin, a sulfur-containing defense compound from garlic, to combat zygomycete fungi. The findings underscore allicin's promise for applications in infections of the nasopharynx via inhalation, suggesting a novel therapeutic avenue against challenging fungal infections.


Assuntos
Infecções Fúngicas Invasivas , Mucorales , Micoses , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Mucorales/metabolismo , Anfotericina B/farmacologia , Ácidos Sulfínicos/farmacologia , Ácidos Sulfínicos/uso terapêutico , Dissulfetos/farmacologia , Micoses/tratamento farmacológico , Infecções Fúngicas Invasivas/tratamento farmacológico
18.
J Agric Food Chem ; 71(49): 19207-19220, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-37943254

RESUMO

Garlic has been used worldwide as a spice due to its pungent taste and flavor-enhancing properties. As a main biologically active component of the freshly crushed garlic extracts, allicin (diallyl thiosulfinate) is converted from alliin by alliinase upon damaging the garlic clove, which has been reported to have many potent beneficial biological functions. In this work, allicin formation, stability, bioavailability, and metabolism process are examined and summarized. The biological functions of allicin and potential underlying mechanisms are reviewed and discussed, including antioxidation, anti-inflammation, antidiabetic, cardioprotective, antineurodegenerative, antitumor, and antiobesity effects. Novel delivery systems of allicin with enhanced stability, encapsulation efficiency, and bioavailability are also evaluated, such as nanoparticles, gels, liposomes, and micelles. This study could provide a comprehensive understanding of the physiochemical properties and health benefits of allicin, with great potential for further applications in the food and nutraceutical industries.


Assuntos
Dissulfetos , Alho , Disponibilidade Biológica , Suplementos Nutricionais , Alho/química , Ácidos Sulfínicos/química , Antioxidantes/metabolismo
19.
J Agric Food Chem ; 71(42): 15785-15795, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37830900

RESUMO

Acrylamide (AA), commonly formed in carbohydrate-rich thermally processed foods, exerts harmful effects on the kidney. Allicin, from crushed garlic cloves, exhibits strong biological activities. In the current study, the protection mechanisms of allicin against AA-caused nephrotoxicity were comprehensively examined using an in vivo rat model based on previous research that allicin plays a key role in improving renal function. The results showed that allicin attenuated histological changes of the kidney and ameliorated renal function. Damaged mitochondrial structures, upregulated voltage-dependent anion channel 1 expression, and decreased membrane potential and adenosine 5'-triphosphate levels were observed after AA treatment. Surprisingly, allicin notably reversed the adverse effects. Further, allicin effectively restored mitochondrial function via modulating mitochondrial biogenesis and dynamics, which might be associated with the upregulated expression of sirtuin 1 (SIRT1). Meanwhile, allicin dramatically activated the SIRT1 activity and subsequently inhibited p53 acetylation, prevented the translocation of cytochrome c to the cytoplasm, and reduced the caspase expression, thus further inhibiting mitochondrial apoptosis caused by AA. In summary, the relieving effect of allicin on AA-caused nephrotoxicity lies in its inhibition of mitochondrial dysfunction and mitochondrial apoptosis.


Assuntos
Acrilamida , Sirtuína 1 , Ratos , Animais , Sirtuína 1/genética , Sirtuína 1/metabolismo , Acrilamida/toxicidade , Acrilamida/metabolismo , Apoptose , Ácidos Sulfínicos/farmacologia , Dissulfetos/metabolismo , Rim/metabolismo , Mitocôndrias/metabolismo
20.
Zhongguo Zhong Yao Za Zhi ; 48(13): 3409-3420, 2023 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-37474979

RESUMO

Cardiovascular diseases(CVD) with high morbidity and mortality pose severe threats to human life. Allicin, a main active ingredient of garlic, possesses multiple pharmaceutical activities. It not only exerts cardioprotective effects but also prevents the risk factors for CVD. Allicin exerts cardioprotective effects via a variety of mechanisms, including inhibiting oxidative stress, apoptosis, autophagy, and inflammatory responses, regulating lipid metabolism and gut microbiota, inducing hydrogen sulfide production, and dilating vessels. Despite the valuable cardioprotective effects, the instability of allicin has hindered the basic research and clinical application. This paper reviews the progress in the cardioprotective effects and mechanisms of allicin in the last decade and summarizes the methods to improve the stability of allicin. In addition, this review provides a reference for further research and development of allicin in cardiovascular protection.


Assuntos
Doenças Cardiovasculares , Dissulfetos , Humanos , Coração , Ácidos Sulfínicos/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Preparações Farmacêuticas
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